scholarly journals Understanding the translocation mechanism of PLGA nanoparticles across round window membrane into the inner ear: a guideline for inner ear drug delivery based on nanomedicine

2018 ◽  
Vol Volume 13 ◽  
pp. 479-492 ◽  
Author(s):  
Liping Zhang ◽  
Yuan Xu ◽  
Wenjuan Cao ◽  
Shibao Xie ◽  
Lu Wen ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Inner Ear ◽  
Round Window ◽  
Plga Nanoparticles ◽  
Round Window Membrane ◽  
Translocation Mechanism

Distribution of PLGA nanoparticles in chinchilla cochleae

2007 ◽  
Vol 137 (4) ◽  
pp. 619-623 ◽  
Author(s):  
Xianxi Ge ◽  
Ronald L. Jackson ◽  
Jianzhong Liu ◽  
Elizabeth A. Harper ◽  
Michael E. Hoffer ◽  
...  
Keyword(s):  
Inner Ear ◽  
Round Window ◽  
Organ Of Corti ◽  
Plga Nanoparticles ◽  
Round Window Membrane ◽  
Scala Tympani ◽  
Magnetic Forces ◽  
Magnetic Exposure ◽  
Transmission Electron ◽  
Electron Energy Loss

Objectives To study the distribution of polylactic/glycolic acid–encapsulated iron oxide nanoparticles (PLGA-NPs) in chinchilla cochleae after application on the round window membrane (RWM). Study Design and Setting Six chinchillas (12 ears) were equally divided into controls (no treatments) and experimen-tals (PLGA-NP with or without magnetic exposure). After 40 minutes of PLGA-NP placement on the RWM, perilymph was withdrawn from the scala tympani. The RWM and cochleae were fixed with 2.5% glutaraldehyde and processed for transmission electron microscopy. Results Nanoparticles were found in cochleae with or without exposure to magnet forces appearing in the RWM, perilymph, endolymph, and multiple locations in the organ of Corti. Electron energy loss spectroscopy confirmed iron elements in nanoparticles. Conclusion The nanoparticles were distributed throughout the inner ear after application on the chinchilla RWM, with and without magnetic forces. Significance PLGA-NP applied to the RWM may have potential for sustained therapy to the inner ear.

Magnetic Assisted Transport of PLGA Nanoparticles Through a Human Round Window Membrane Model

2010 ◽  
Vol 1 (3) ◽  
Author(s):  
Xinsheng Gao ◽  
Youdan Wang ◽  
Kejian Chen ◽  
Brian P. Grady ◽  
Kenneth J. Dormer ◽  
...  
Keyword(s):  
Magnetic Field ◽  
Drug Delivery ◽  
Permanent Magnets ◽  
Round Window ◽  
Superparamagnetic Iron Oxide ◽  
Clinical Problem ◽  
Plga Nanoparticles ◽  
Round Window Membrane ◽  
Water Emulsion ◽  
Coumarin 6

The lack of an effective method for inner ear drug delivery is a clinical problem for the prevention and treatment of hearing loss. With technology advances in nanomedicine and the use of hydrogels, more drug delivery options are becoming available. This study tested the feasibility of using a tripartite layer round window membrane (RWM) model to evaluate the effectiveness of a magnetic assisted transport of poly(lactic-co-glycolic acid) (PLGA)/superparamagnetic iron oxide nanoparticles (SPIONs). A RWM model was constructed as a three-cell-layer model with epithelial cells cultured on both sides of a small intestinal submucosal (SIS) matrix with fibroblasts seeded within the matrix. PLGA encapsulated coumarin-6/SPION nanoparticles 100 nm in diameter were formulated by an oil-in-water emulsion/solvent evaporation method and pulled through the RWM model using permanent magnets with a flux density 0.410 T at the pole face. Independent variables such as external magnetic force and exposure time, composition of hyaluronic acid (HA) hydrogel suspending media, and particle characteristics including magnetic susceptibility were studied. Magnetic assisted transport of coumarin-6 labeled magnetic nanoparticles through the RWM inserts increased 2.1-fold in 1 h compared with the controls. HA hydrogel did prevent particle accumulation on the surface of RWM in a magnetic field but also impaired the mobility of these particles. Greater particle susceptibility or stronger external magnetic fields did not significantly improve the transmembrane transport. A RWM model was designed consisting of a SIS membrane and three co-cultured layers of cells, which was structurally and physically similar to the human. PLGA particles (100 nm) with encapsulated ∼15 nm SPIONs were transported through this model with the assistance of an external magnet, allowing quantitative evaluation of prospective targeted drug delivery through the RWM via the assistance of a magnetic field.

scholarly journals Determination of the Round Window Niche Anatomy Using Cone Beam Computed Tomography Imaging as Preparatory Work for Individualized Drug-Releasing Implants

2021 ◽  
Vol 7 (5) ◽  
pp. 79
Author(s):  
Farnaz Matin ◽  
Ziwen Gao ◽  
Felix Repp ◽  
Samuel John ◽  
Thomas Lenarz ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Drug Delivery ◽  
Inner Ear ◽  
Cone Beam Computed Tomography ◽  
Round Window ◽  
Local Drug Delivery ◽  
Cone Beam ◽  
Round Window Membrane ◽  
Round Window Niche ◽  
Bony Overhang

Modern therapy of inner ear disorders is increasingly shifting to local drug delivery using a growing number of pharmaceuticals. Access to the inner ear is usually made via the round window membrane (RWM), located in the bony round window niche (RWN). We hypothesize that the individual shape and size of the RWN have to be taken into account for safe reliable and controlled drug delivery. Therefore, we investigated the anatomy and its variations. Cone beam computed tomography (CBCT) images of 50 patients were analyzed. Based on the reconstructed 3D volumes, individual anatomies of the RWN, RWM, and bony overhang were determined by segmentation using 3D SlicerTM with a custom build plug-in. A large individual anatomical variability of the RWN with a mean volume of 4.54 mm3 (min 2.28 mm3, max 6.64 mm3) was measured. The area of the RWM ranged from 1.30 to 4.39 mm2 (mean: 2.93 mm2). The bony overhang had a mean length of 0.56 mm (min 0.04 mm, max 1.24 mm) and the shape was individually very different. Our data suggest that there is a potential for individually designed and additively manufactured RWN implants due to large differences in the volume and shape of the RWN.

scholarly journals Cutaneous and Labyrinthine Tolerance of Bioactive Glass S53P4 in Mastoid and Epitympanic Obliteration Surgery: Prospective Clinical Study

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Daniele Bernardeschi ◽  
Yann Nguyen ◽  
Francesca Yoshie Russo ◽  
Isabelle Mosnier ◽  
Evelyne Ferrary ◽  
...  
Keyword(s):  
Bioactive Glass ◽  
Inner Ear ◽  
Round Window ◽  
Bone Conduction ◽  
Hearing Threshold ◽  
Round Window Membrane ◽  
Prospective Clinical Study ◽  
Local Skin ◽  
Local Skin Reaction ◽  
Bone Conduction Hearing

Objective. To evaluate the cutaneous and the inner ear tolerance of bioactive glass S53P4 when used in the mastoid and epitympanic obliteration for chronic otitis surgery.Material and Methods. Forty-one cases have been included in this prospective study. Cutaneous tolerance was clinically evaluated 1 week, 1 month, and 3 months after surgery with a physical examination of the retroauricular and external auditory canal (EAC) skin and the presence of otalgia; the inner ear tolerance was assessed by bone-conduction hearing threshold 1 day after surgery and by the presence of vertigo or imbalance.Results. All surgeries but 1 were uneventful: all patients maintained the preoperative bone-conduction hearing threshold except for one case in which the round window membrane was opened during the dissection of the cholesteatoma in the hypotympanum and this led to a dead ear. No dizziness or vertigo was reported. Three months after surgery, healing was achieved in all cases with a healthy painless skin. No cases of revision surgery for removal of the granules occurred in this study.Conclusion. The bioactive glass S53P4 is a well-tolerated biomaterial for primary or revision chronic otitis surgery, as shown by the local skin reaction which lasted less than 3 months and by the absence of labyrinthine complications.

Inner Ear Pathology and Otitis Media

1980 ◽  
Vol 89 (3_suppl) ◽  
pp. 249-253 ◽  
Author(s):  
Michael M. Paparella ◽  
Marcos V. Goycoolea ◽  
William L. Meyerhoff
Keyword(s):  
Inner Ear ◽  
Otitis Media ◽  
Round Window ◽  
Round Window Membrane

Insidious inner ear complications of otitis media have been and are being studied in our laboratory. The purpose of this paper is to review these studies, coordinate, capsulize and highlight the results with emphasis on the transport role of the round window membrane.

scholarly journals A Totally Implantable Drug Delivery System for Local Therapy of the Middle and Inner Ear

1997 ◽  
Vol 76 (8) ◽  
pp. 567-570 ◽  
Author(s):  
Rolf Lehner ◽  
Heribert Brugger ◽  
Marcus M. Maassen ◽  
Hans-Peter Zenner
Keyword(s):  
Drug Delivery ◽  
Inner Ear ◽  
Drug Delivery System ◽  
Delivery System ◽  
Drug Application ◽  
Local Therapy ◽  
Trophic Factors ◽  
Mastoid Cavity ◽  
Round Window Membrane ◽  
Wide Range

Local therapy of middle and inner ear diseases is being used, but is restricted to cases of ear drum perforation or to repeated invasive intratympanic drug application by the physician. In accordance with the Medical Device Directive (class III), a bone-anchored, totally implantable drug delivery system (TI-DDS) has been developed. It includes a micropump for subcutaneous, patient-controlled activation, a drug reservoir and a septum port. A thin guide-wired catheter leads from the pump outlet to the point of application in the mastoid or middle ear cavities. Local inner ear therapy with suitable drugs is possible by positioning the catheter's end near the round window membrane. The system requires no battery and will offer a wide range of patient-controlled bolus applications (25 μl per activation). We first analyzed the three-dimensional implantation geometry of the mastoid cavity. Basic micromechanical problems have been solved in order to create several prototypes. The TI-DDS has already undergone extensive in vitro testing. Recent results of pump rate precision and digital pressure force testing are promising. Local drug treatment for conditions such as lidocaine-sensitive tinnitus, secretory otitis media, Meniere's disease, localized pain and intralesional cancer is under discussion. Furthermore, local application of future biotechnological trophic factors for inner ear treatment is anticipated. The basic engineering is completed and initial animal tests are in preparation.

Eradicating Otomycosis with Terbinafine Solution: Basic and Clinical Investigation

2019 ◽  
Vol 24 (4) ◽  
pp. 183-190
Author(s):  
Ting-Hua Yang ◽  
Yi-Ho Young
Keyword(s):  
Clinical Practice ◽  
Inner Ear ◽  
Morphological Study ◽  
Antifungal Agents ◽  
Clinical Investigation ◽  
Round Window ◽  
Round Window Membrane ◽  
Potential Candidate ◽  
Potential Treatment ◽  
Total Dosage

Background: Otomycosis still remains intractable in clinical practice, likely because topical antifungal agents lack efficacy or are potentially toxic to the inner ear end organs. Objectives: The aim of this study was to investigate whether terbinafine solution is a potential candidate for treating intractable otomycosis in humans. In addition, the toxic effect on the inner ear was also assessed by animal models treated with terbinafine. Methods: Guinea pigs were instilled with 0.1 mL terbinafine (10 and 25 mg/mL) in the left round window membrane. At 2 weeks after treatment, all animals underwent an inner ear test battery and were then sacrificed for morphological study. Clinically, 20 patients with otomycosis were treated with terbinafine solution at a dosage of 0.4 mg. Results: All terbinafine-treated animals showed intact inner ear function when total dosage of terbinafine was <2.5 mg, which was further confirmed by morphological study. Subsidence of otomycosis was achieved in all 20 patients 1 week after treatment with terbinafine (0.4 mg) without untoward effect. No evidence of recurrence was noted 1 year after treatment. Conclusion: The paucity of inner ear toxicity of terbinafine even at a dosage of 2.5 mg was identified in guinea pig models morphologically and physiologically. Topical application of terbinafine solution at a dosage of 0.4 mg may be a potential treatment for otomycosis in humans.

Intratympanic Steroid Treatment of Inner Ear Disease and Tinnitus (Preliminary Report)

1996 ◽  
Vol 75 (8) ◽  
pp. 468-488 ◽  
Author(s):  
Herbert Silverstein ◽  
Daniel Choo ◽  
Seth I. Rosenberg ◽  
Jeffery Kuhn ◽  
Michael Seidman ◽  
...  
Keyword(s):  
Inner Ear ◽  
Round Window ◽  
Meniere’S Disease ◽  
Menière’S Disease ◽  
Round Window Membrane ◽  
Meniere's Disease ◽  
Ménière’S Disease ◽  
Menière's Disease ◽  
Inner Ear Disease ◽  
Ménière's Disease

Intratympanic instillation of Depo-Medrol® (80 mg/cc), dexamethasone ophthalmic solution (1 mg/cc), or dexamethasone intravenous (4 mg/cc) solution produces improvement of cochlear function in certain patients with Meniere's disease, autoimmune inner ear disease and sudden sensorineural deafness. Tinnitus improved in 47%, most often in patients with Meniere's disease (9 of 15; 60%). The SRT improvement of greater than 10 dB or SD greater than 15% was documented in 41% (average improvement in SRT: 15 dB; SD: 24%). Patients with tinnitus and bilateral sensorineural hearing loss (i.e., presbycusis) did not benefit from the treatment. Prior to treatment with intratympanic medication, laser-assisted tympanostomy with middle ear exploration, using otoendoscopy to determine the status of the round window niche and remove mucosal folds, helps in making the round window membrane accessible to local application of drops. Placing Gelfoam into the round window niche under direct vision, and using a Venturi Bobbin tube in the tympanic membrane, appears to be a satisfactory method for delivering medication to the inner ear fluids. The medication can be injected by the physician through the tube into the middle ear, or the patient can perform self-treatment at home, placing medication in the external auditory canal. A double-blind, cross-over study in patients with Meniere's disease is now in progress with Institutional Review Board (IRB) approval, which will be reported at a later date. This preliminary study has shown that intratympanic steroids may affect the symptoms of hearing loss and tinnitus in patients with various inner ear problems. Patients with Meniere's disease appear to respond in the highest percentage of cases. Hopefully, additional research will suggest the appropriate drugs which can be used to treat inner ear disease. Direct application of the drug to the round window membrane may increase the concentration in the inner ear fluids, thus avoiding the systemic effects.

Inner ear biocompatibility of lipid nanocapsules after round window membrane application

2011 ◽  
Vol 404 (1-2) ◽  
pp. 211-219 ◽  
Author(s):  
Ya Zhang ◽  
Weikai Zhang ◽  
Marian Löbler ◽  
Klaus-Peter Schmitz ◽  
Patrick Saulnier ◽  
...  
Keyword(s):  
Inner Ear ◽  
Round Window ◽  
Round Window Membrane ◽  
Lipid Nanocapsules

scholarly journals Effect of oxygen-flooding to the round window membrane on the inner ear function of the anoxic cochlea.

1986 ◽  
Vol 79 (7) ◽  
pp. 1143-1147
Author(s):  
Toshimitsu KOBAYASHI ◽  
Takuji OKITSU ◽  
Katsuhisa IKEDA ◽  
Jun KUSAKARI
Keyword(s):  
Inner Ear ◽  
Round Window ◽  
Round Window Membrane ◽  
Effect Of Oxygen
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